乌司他丁复合帕瑞昔布钠对老年患者髋关节置换术后早期细胞免疫及认知功能的影响

Effects of ulinastatin with parecoxib sodium on early cellular immunology function and cognitive function in elderly patients undergoing total hip replacement

目的探讨乌司他丁联合帕瑞昔布钠对老年患者单侧髋关节置换术后早期细胞免疫及认知功能的影响。方法选择择期行单侧髋关节置换术患者100例,性别不限,年龄65~80岁,随机分为四组:乌司他丁组(W组)、帕瑞昔布钠组(P组、乌司他丁联合帕瑞昔布钠组(WP组)和生理盐水对照组(C组),每组25例。W组于切皮前、手术结束即刻分别给予乌司他丁5 000U/kg;P组于麻醉诱导前给予帕瑞昔布钠40mg,之后40mg/12h,共6次;WP组于切皮前、手术结束即刻分别给予乌司他丁5 000U/kg,30min内泵注完毕,并于麻醉诱导前给予帕瑞昔布钠40mg,之后40mg/12h,共6次;C组于相同时点给予等量生理盐水。记录患者手术时间、术中出血量、自体血输注量和芬太尼总用量;于入室前(T_0)、术毕(T_1)、术后6h(T_2)、24h(T_3)及72h(T_4)采集外周静脉血,采用流式细胞术检测血T淋巴细胞(CD3^+、CD4^+、CD8^+),计算CD4^+/CD8^+值,同时采用ELISA法测定各时点血清IL-6、TNF-α、神经元特异性烯醇化酶(NSE)浓度和S100β蛋白含量。分别于T_0、T_4和术后7d(T5)时对患者进行简易智能状态量表(MMSE)评分。结果与T_0时比较,C、W和P组T_1~T_4时CD3^+、CD4^+细胞含量及CD4^+/CD8^+值明显降低,IL-6和TNF-α浓度明显升高,T_2、T_3时NSE浓度和S100β蛋白含量明显升高(P<0.05);T_2、T_3时W和P组,T_1~T_4时WP组CD3^+、CD4^+细胞含量及CD4^+/CD8^+值明显高于,IL-6、TNF-α、NSE浓度和S100β蛋白含量明显低于C组(P<0.05);T_2、T_3时WP组CD3^+、CD4^+细胞含量及CD4^+/CD8^+值明显高于,IL-6、TNF-α、NSE浓度和S100β蛋白含量明显低于W和P组(P<0.05)。与T_0时比较,T_4、T5时C组MMSE评分明显降低(P<0.05);T_4时W、P和WP组MMSE评分明显高于C组(P<0.05);T_4时WP组患者MMSE评分明显高于W和P组(P<0.05)。结论乌司他丁联合帕瑞昔布钠可改善老年患者单侧髋关节置换术细胞免疫功能及认知功能,较单独使用效果更好。

Objective To investigate the effects of ulinastatin with parecoxib sodium on early cellular immunology function and cognitive function in elderly patients undergoing total hip replacement.Methods One hundred patients（aged 65-80 years,ASA grade Ⅱ）undergoing elective total hip replacement were randomly assigned into 4groups：group W（n=25）,group P（n=25）,group WP（n=25）and group C（n =25）.The patients in group W received intravenous injection of ulinastatin with a dose of 5 000U/kg before skin incision and at the moment of the end of operation.Patients in group P accepted intravenous injection of parecoxib sodium of 40 mg before anesthesia and at a 12 hintervals for six times.Patients in group WP accepted intravenous injection of ulinastatin with a dose of 5 000U/kg before skin incision and at the moment of the end of operation,and accepted intravenous injection of parecoxib sodium with a dose of 40 mg before anesthesia and at a 12 hinterval for six times.Patients in group C were given normal saline at the same time as placebo.The operation time,the volume of bleeding and autologous blood receiving and the intraoperative fentanyl consumption were recorded in four groups.Blood samples were obtained before induction（T_0）,at the end of operation（T_1）,on 6h（T_2）,24h（T_3）,72h（T_4）after operation for determination of plasma concentration of S100βprotein,neuron-specific enolase（NSE）,IL-6,TNF-α.The percentages of T lymphocyte subsets（CD3^＋,CD4^＋,CD8^＋）and CD4^＋/CD8^＋ratio were detected with flow cytometry.The Mini-Mental State Examination（MMSE）was used to test the cognitive function of the patients at T_0,T_4 and 7dafter operation（T5）.Results Compared with T_0,the percentages of CD3^＋,CD4^＋cells and CD4^＋/CD8^＋in groups C,W and P were significantly decreased,the plasma concentrations of IL-6and TNF-αsignificantly increased at T_1-T_4,concentration of NSE and S100 protein were significantly increased at T_2 and T_3（P〈0.05）.the percentages of CD3^＋,CD4^＋T lymphocyte and CD4^＋/CD8^＋ratio in groups W and P at T_2,T_3 and group WP at T_1-T_4 was significantly higher than that of group C,the concentration of IL-6,TNF-α,NSE and S100βprotein content was significantly lower than in group C（P〈0.05）;the percentages of CD3^＋,CD4^＋T lymphocyte and CD4^＋/CD8^＋ratio in group WP was significantly higher than those of groups W and P,the concentrations of TNF-α,IL-6,NSE and S100βprotein content was significantly lower than those of group W and P at T_2,T_3（P〈0.05）.Compared with T_0,MMSE score in group C was significantly lower at T_4,T_5（P〈0.05）.MMSE score of groups W,P and WP was significantly higher than that of group C at T_4（P〈0.05）.MMSE score of group WP was significantly higher than those of groups W and P at T_4（P〈0.05）.Conclusion Ulinastatin combined with parecoxib sodium ameliorates early cellular immunology function and cognitive function in elderly patients undergoing total hip replacement,and it is more effective than using ulinastatin or parecoxib sodium alone.